tbuckley/cabot-search huggingface dataset:
Hypoxic Microenvironment Reconstruction with Synergistic Biofunctional Ions Promotes Diabetic Wound Healing
Authors: Xiaochen Chen, Liyan Zhang, Wenwen Chai, Pengfei Tian, Jua Kim, Jingxin Ding, Hao Zhang, Chunyu Liu, Deping Wang, Xu Cui, Haobo Pan
Journal: Advanced Healthcare Materials (2023)

Abstract Chronic hypoxia and ischemia make diabetic wounds non‐healing. Cellular functions of diabetic chronic wounds are inhibited under a pathological environment. Therefore, this work develops a composite hydrogel system to promote diabetic wound healing. The composite hydrogel system consists of ε‐poly‐lysine (EPL), calcium peroxide (CP), and borosilicate glass (BG). The hydrogel supplies continuous dissolved oxygen molecules to the wound that can penetrate the skin tissue to restore normal cellular function and promote vascular regeneration. Biofunctional ions released from BGs can recruit more macrophages through neovascularization and modulate macrophage phenotypic transformation. Combining oxygen‐mediated vascular regeneration and ion‐mediated inflammatory regulation significantly accelerated diabetic wound healing. These findings indicate that this composite hydrogel system holds promise as a novel tissue engineering material.
Combination of chemotherapy and all-trans retinoic acid for the treatment KMT2A-rearranged infant acute lymphoblastic leukemia. Results of the MLL-Baby trial
Authors: Larisa Fechina, Alexander Popov, Grigory Tsaur, Guenter Henze, Egor Shorikov, Olga Makarova, Olga Khlebnikova, Yulia Zhukova, Oleg Arakaev, Olga Streneva, Tatiana Verzhbitskaya, Tatiana Riger, Alexander Solodovnikov, Elena Lapotentova, Olga Aleinikova, Natalia Myakova, Elmira Boichenko, Konstantin Kondratchik, Olga Nikonova, Alexander Shapochnik, Marina Goroshkova, Natalia Ponomareva, Galina Novichkova, Alexander Karachunskiy, Alexander Roumiantsev
Journal: Leukemia (2023)
Surfactant-like photosensitizer for endoscopic duodenal ablation: Modulating meal-stimulated incretin hormones in obese and type 2 diabetes
Authors: Sanghee Lee, Moon Jae Chung, Minji Ahn, Hyun Jin Park, Eun Kyung Wang, Taeeun Guon, Hyun Jung Kee, Cheol Ryong Ku, Kun Na
Journal: Biomaterials (2023)
Synchrotron microtomography reveals insights into the degradation kinetics of bio-degradable coronary magnesium scaffolds
Authors: Roman Menze, Bernhard Hesse, Maciej Kusmierczuk, Duote Chen, Timm Weitkamp, Stephanie Bettink, Bruno Scheller
Journal: Bioactive Materials (2023)

Bioresorbable magnesium scaffolds are a promising future treatment option for coronary artery stenosis, especially for young adults. Due to the degradation of these scaffolds (<1 year), long-term device-related clinical events could be reduced compared to treatments with conventional drug eluting stents. First clinical trials indicate a return of vasomotion after one year, which may be associated with improved long-term clinical outcomes. However, even after decades of development, the degradation process, ideal degradation time and biological response in vivo are still not fully understood. The present study investigates the in vivo degradation of magnesium scaffolds in the coronary arteries of pigs influenced by different strut thicknesses and the presence of antiproliferative drugs. Due to high 3D image contrast of synchrotron-based micro-CT with phase contrast (SR-μCT), a qualitative and quantitative evaluation of the degradation morphology of magnesium scaffolds was obtained. For the segmentation of the μCT images a convolutional network architecture (U-net) was exploited, demonstrating the huge potential of merging high resolution SR-μCT with deep learning (DL) supported data analysis. In total, 30 scaffolds, made of the rare earth alloy Resoloy®, with different strut designs were implanted into the coronary arteries of 10 domestic pigs for 28 days using drug-coated or uncoated angioplasty balloons for post-dilatation. The degradation morphology was analyzed using scanning electron microscopy, energy dispersive x-ray spectroscopy and SR-μCT. The data from these methods were then related to data from angiography, optical coherence tomography and histology. A thinner strut size (95 vs. 130 μm) and the presence of paclitaxel indicated a slower degradation rate at 28 d in vivo, which positively influences the late lumen loss (0.5 and 0.6 mm vs. 1.0 and 1.1 mm) and recoil values (0 and 1.7% vs. 6.1 and 22%).
Dupilumab alleviates pruritus regardless of skin improvement in adults with atopic dermatitis: A cohort study
Authors: Yun-Wen Chen, Hsin-Hua Chen, Wen-Nan Huang, Chiann-Yi Hsu, Yi-Hsing Chen, Wei-Ting Hung, Kuo-Tung Tang
Journal: Journal of the American Academy of Dermatology (2023)
Vepafestinib is a pharmacologically advanced RET-selective inhibitor with high CNS penetration and inhibitory activity against RET solvent front mutations
Authors: Isao Miyazaki, Igor Odintsov, Keiji Ishida, Allan J. W. Lui, Masanori Kato, Tatsuya Suzuki, Tom Zhang, Kentaro Wakayama, Renate I. Kurth, Ryan Cheng, Hidenori Fujita, Lukas Delasos, Morana Vojnic, Inna Khodos, Yukari Yamada, Kota Ishizawa, Marissa S. Mattar, Kaoru Funabashi, Qing Chang, Shuichi Ohkubo, Wakako Yano, Ryuichiro Terada, Claudio Giuliano, Yue Christine Lu, Annalisa Bonifacio, Siddharth Kunte, Monika A. Davare, Emily H. Cheng, Elisa de Stanchina, Emanuela Lovati, Yoshikazu Iwasawa, Marc Ladanyi, Romel Somwar
Journal: Nature Cancer (2023)

Abstract RET receptor tyrosine kinase is activated in various cancers (lung, thyroid, colon and pancreatic, among others) through oncogenic fusions or gain-of-function single-nucleotide variants. Small-molecule RET kinase inhibitors became standard-of-care therapy for advanced malignancies driven by RET. The therapeutic benefit of RET inhibitors is limited, however, by acquired mutations in the drug target as well as brain metastasis, presumably due to inadequate brain penetration. Here, we perform preclinical characterization of vepafestinib (TAS0953/HM06), a next-generation RET inhibitor with a unique binding mode. We demonstrate that vepafestinib has best-in-class selectivity against RET, while exerting activity against commonly reported on-target resistance mutations (variants in RET L730 , RET V804 and RET G810 ), and shows superior pharmacokinetic properties in the brain when compared to currently approved RET drugs. We further show that these properties translate into improved tumor control in an intracranial model of RET-driven cancer. Our results underscore the clinical potential of vepafestinib in treating RET-driven cancers.
Impact of milk secretor status on the fecal metabolome and microbiota of breastfed infants
Authors: Aidong Wang, Aly Diana, Sofa Rahmannia, Rosalind S Gibson, Lisa A Houghton, Carolyn M Slupsky
Journal: Gut Microbes (2023)

Maternal secretor status has been shown to be associated with the presence of specific fucosylated human milk oligosaccharides (HMOs), and the impact of maternal secretor status on infant gut microbiota measured through 16s sequencing has previously been reported. None of those studies have confirmed exclusive breastfeeding nor investigated the impact of maternal secretor status on gut microbial fermentation products. The present study focused on exclusively breastfed (EBF) Indonesian infants, with exclusive breastfeeding validated through the stable isotope deuterium oxide dose-to-mother (DTM) technique, and the impact of maternal secretor status on the infant fecal microbiome and metabolome. Maternal secretor status did not alter the within-community (alpha) diversity, between-community (beta) diversity, or the relative abundance of bacterial taxa at the genus level. However, infants fed milk from secretor (Se+) mothers exhibited a lower level of fecal succinate, amino acids and their derivatives, and a higher level of 1,2-propanediol when compared to infants fed milk from non-secretor (Se-) mothers. Interestingly, for infants consuming milk from Se+ mothers, there was a correlation between the relative abundance of Bifidobacterium and Streptococcus, and between each of these genera and fecal metabolites that was not observed in infants receiving milk from Se- mothers. Our findings indicate that the secretor status of the mother impacts the gut microbiome of the exclusively breastfed infant.
Photoacoustic Imaging Endometriosis Lesions with Nanoparticulate Polydopamine as a Contrast Agent
Authors: Quanjie Lv, Yili Zhang, Ruihao Yang, Yingfan Dai, Yu Lin, Kang Sun, Hong Xu, Ke Tao
Journal: Advanced Healthcare Materials (2023)

Endometriosis (EM) is a prevalent and debilitating gynecological disorder primarily affecting women of reproductive age. The diagnosis of EM is historically hampered by delays, owing to the absence of reliable diagnostic and monitoring techniques. Herein, it is reported that photoacoustic imaging can be a noninvasive modality for deep-seated EM by employing a hyaluronic-acid-modified polydopamine (PDA@HA) nanoparticle as the contrast agent. The PDA@HA nanoparticles exhibit inherent absorption and photothermal effects when exposed to near-infrared light, proficiently converting thermal energy into sound waves. Leveraging the targeting properties of HA, distinct photoacoustic signals emanating from the periphery of orthotopic EM lesions are observed. These findings are corroborated through anatomical observations and in vivo experiments involving mice with green fluorescent protein-labeled EM lesions. Moreover, the changes in photoacoustic intensity over a 24 h period reflect the dynamic evolution of PDA@HA nanoparticle biodistribution. Through the utilization of a photoacoustic ultrasound modality, in vivo assessments of EM lesion volumes are conducted. This innovative approach not only facilitates real-time monitoring of the therapeutic kinetics of candidate drugs but also obviates the need for the sacrifice of experimental mice. As such, this study presents a promising avenue for enhancing the diagnosis and drug-screening processes of EM.
Alterations of milk oligosaccharides in mothers with gestational diabetes mellitus impede colonization of beneficial bacteria and development of RORγt <sup>+</sup> Treg cell-mediated immune tolerance in neonates
Authors: Xinke Li, Xixi Ning, Binqi Rui, Yushuang Wang, Zengjie Lei, Da Yu, Feitong Liu, Yanjie Deng, Jieli Yuan, Wenzhe Li, Jingyu Yan, Ming Li
Journal: Gut Microbes (2023)

Gestational diabetes mellitus (GDM) is an increasing public health concern that significantly increases the risk of early childhood allergic diseases. Altered maternal milk glycobiome may strongly affect gut microbiota and enteric-specific Treg cell-mediated development of immune tolerance in GDM infants. In this study, we found that, compared with healthy Chinese mothers, mothers with GDM had significantly lower levels of total and specific human milk oligosaccharides (HMOs) in their colostrum that subsequently increased with extension of lactation. This alteration in HMO profiles significantly delayed colonization of Lactobacillus and Bifidobacterium spp. in their breast-fed infants, resulting in a distinct gut microbial structure and metabolome. Further experiments in GDM mouse models indicated that decreased contents of milk oligosaccharides, mainly 3'-sialyllactose (3'-SL), in GDM maternal mice reduced colonization of bacteria, such as L. reuteri and L. johnsonii, in the neonatal gut, which impeded development of RORγt+ regulatory T (Treg) cell-mediated immune tolerance. Treatment of GDM neonates with 3'-SL, Lactobacillus reuteri (L. reuteri) and L. johnsonii promoted the proliferation of enteric Treg cells and expression of transcription factor RORγt, which may have contributed to compromising ovalbumin (OVA)-induced allergic responses. In vitro experiments showed that 3'-SL, metabolites of L. johnsonii, and lysates of L. reuteri stimulated differentiation of mouse RORγt+ Treg cells through multiple regulatory effects on Toll-like receptor, MAPK, p53, and NOD-like receptor signaling pathways. This study provides new ideas for the development of gut microbiota and immune tolerance in GDM newborns.
Recent Development of Copper‐Based Nanozymes for Biomedical Applications
Authors: Xin Yu, Yawen Wang, Jian Zhang, Jing Liu, Aizhu Wang, Longhua Ding
Journal: Advanced Healthcare Materials (2023)

Copper (Cu), an indispensable trace element within the human body, serving as an intrinsic constituent of numerous natural enzymes, carrying out vital biological functions. Furthermore, nanomaterials exhibiting enzyme-mimicking properties, commonly known as nanozymes, possess distinct advantages over their natural enzyme counterparts, including cost-effectiveness, enhanced stability, and adjustable performance. These advantageous attributes have captivated the attention of researchers, inspiring them to devise various Cu-based nanomaterials, such as copper oxide, Cu metal-organic framework, and CuS, and explore their potential in enzymatic catalysis. This comprehensive review encapsulates the most recent advancements in Cu-based nanozymes, illuminating their applications in the realm of biochemistry. Initially, it is delved into the emulation of typical enzyme types achieved by Cu-based nanomaterials. Subsequently, the latest breakthroughs concerning Cu-based nanozymes in biochemical sensing, bacterial inhibition, cancer therapy, and neurodegenerative diseases treatment is discussed. Within this segment, it is also explored the modulation of Cu-based nanozyme activity. Finally, a visionary outlook for the future development of Cu-based nanozymes is presented.
ACP‐Mediated Phase Transformation for Collagen Mineralization: A New Understanding of the Mechanism
Authors: Songzhe Shan, Zhenhang Tang, Kaida Sun, Wenjing Jin, Haihua Pan, Ruikang Tang, Wei Yin, Zhijian Xie, Zhuo Chen, Changyu Shao
Journal: Advanced Healthcare Materials (2023)

Despite significant efforts utilizing advanced technologies, the contentious debate surrounding the intricate mechanism underlying collagen fibril mineralization, particularly with regard to amorphous precursor infiltration and phase transformation, persists. This work proposes an amorphous calcium phosphate (ACP)-mediated pathway for collagen fibril mineralization and utilizing stochastic optical reconstruction microscopy technology, and has experimentally confirmed for the first time that the ACP nanoparticles can infiltrate inside collagen fibrils. Subsequently, the ACP-mediated phase transformation occurs within collagen fibrils to form HAP crystallites, and significantly enhances the mechanical properties of the mineralized collagen fibrils compared to those achieved by the calcium phosphate ion (CPI)-mediated mineralization and resembles the natural counterpart. Furthermore, demineralized dentin can be effectively remineralized through ACP-mediated mineralization, leading to complete restoration of its mechanical properties. This work provides a new paradigm of collagen mineralization via particle-mediated phase transformation, deepens the understanding of the mechanism behind the mineralization of collagen fibrils, and offers a new strategy for hard tissue repair.
Mitochondrial Artificial K<sup>+</sup> Channel Construction Using MPTPP@5F8 Nanoparticles for Overcoming Cancer Drug Resistance via Disrupting Cellular Ion Homeostasis
Authors: Panqin Ma, Zheng Luo, Zhiguo Li, Yuchao Lin, Zibiao Li, Zhen Wu, Changliang Ren, Yun‐Long Wu
Journal: Advanced Healthcare Materials (2023)

Mitochondrial potassium ion channels have become a promising target for cancer therapy. However, in malignant tumors, their low expression or inhibitory regulation typically leads to undesired cancer therapy, or even induces drug resistance. Herein, this work develops an in situ mitochondria-targeted artificial K
When science and evidence is not enough: challenging the recommendations from the Commission on Human Medicines Isotretinoin Expert Working Group
Authors: Eugene Tan, Harriet Kennedy, Marius Rademaker
Journal: British Journal of Dermatology (2023)

The Commission on Human Medicines (CHM) Isotretinoin Expert Working Group recently released a report with several major recommendations. The authors scrutinized the evidence cited by the CHM and presented the case that their recommendations undermine evidence-based medicine and scientific thinking.
Spray dried lipid nanoparticle formulations enable intratracheal delivery of mRNA
Authors: Kristina Pagh Friis, Sandra Gracin, Steven Oag, Alexandra Leijon, Elin Sand, Botilda Lindberg, Elisa Lázaro-Ibáñez, Johnny Lindqvist, Kathryn A. Whitehead, Annette Bak
Journal: Journal of Controlled Release (2023)
Circulating GDF11 exacerbates myocardial injury in mice and associates with increased infarct size in humans
Authors: Simon Kraler, Carolina Balbi, Daria Vdovenko, Tetiana Lapikova-Bryhinska, Giovanni G Camici, Luca Liberale, Nicole Bonetti, Candela Diaz Canestro, Fabienne Burger, Aline Roth, Federico Carbone, Giuseppe Vassalli, François Mach, Shalender Bhasin, Florian A Wenzl, Olivier Muller, Lorenz Räber, Christian M Matter, Fabrizio Montecucco, Thomas F Lüscher, Alexander Akhmedov
Journal: Cardiovascular Research (2023)

Abstract Aims The heart rejuvenating effects of circulating growth differentiation factor 11 (GDF11), a transforming growth factor-β superfamily member that shares 90% homology with myostatin (MSTN), remains controversial. Here, we aimed to probe the role of GDF11 in acute myocardial infarction (MI), a frequent cause of heart failure and premature death during ageing. Methods and results In contrast to endogenous Mstn, myocardial Gdf11 declined during the course of ageing and was particularly reduced following ischaemia/reperfusion (I/R) injury, suggesting a therapeutic potential of GDF11 signalling in MI. Unexpectedly, boosting systemic Gdf11 by recombinant GDF11 delivery (0.1 mg/kg body weight over 30 days) prior to myocardial I/R augmented myocardial infarct size in C57BL/6 mice irrespective of their age, predominantly by accelerating pro-apoptotic signalling. While intrinsic cardioprotective signalling pathways remained unaffected by high circulating GDF11, targeted transcriptomics and immunomapping studies focusing on GDF11-associated downstream targets revealed attenuated Nkx2-5 expression confined to CD105-expressing cells, with pro-apoptotic activity, as assessed by caspase-3 levels, being particularly pronounced in adjacent cells, suggesting an indirect effect. By harnessing a highly specific and validated liquid chromatography-tandem mass spectrometry–based assay, we show that in prospectively recruited patients with MI circulating GDF11 but not MSTN levels incline with age. Moreover, GDF11 levels were particularly elevated in those at high risk for adverse outcomes following the acute event, with circulating GDF11 emerging as an independent predictor of myocardial infarct size, as estimated by standardized peak creatine kinase-MB levels. Conclusion Our data challenge the initially reported heart rejuvenating effects of circulating GDF11 and suggest that high levels of systemic GDF11 exacerbate myocardial injury in mice and humans alike. Persistently high GDF11 levels during ageing may contribute to the age-dependent loss of cardioprotective mechanisms and thus poor outcomes of elderly patients following acute MI.
Nano transdermal system combining mitochondria-targeting cerium oxide nanoparticles with all-trans retinoic acid for psoriasis
Authors: Wei Wang, Xinyi Xu, Yanling Song, Lan Lan, Jun Wang, Xinchang Xu, Yongzhong Du
Journal: Asian Journal of Pharmaceutical Sciences (2023)

Psoriasis is an inflammatory skin disease that is intricately linked to oxidative stress. Antioxidation and inhibition of abnormal proliferation of keratinocytes are pivotal strategies for psoriasis. Delivering drugs with these effects to the site of skin lesions is a challenge that needs to be solved. Herein, we reported a nanotransdermal delivery system composed of all-trans retinoic acid (TRA), triphenylphosphine (TPP)-modified cerium oxide (CeO2) nanoparticles, flexible nanoliposomes and gels (TCeO2-TRA-FNL-Gel). The results revealed that TCeO2 synthesized by the anti-micelle method, with a size of approximately 5 nm, possessed excellent mitochondrial targeting ability and valence conversion capability related to scavenging reactive oxygen species (ROS). TCeO2-TRA-FNL prepared by the film dispersion method, with a size of approximately 70 nm, showed high drug encapsulation efficiency (>96%). TCeO2-TRA-FNL-Gel further showed sustained drug release behaviors, great transdermal permeation ability, and greater skin retention than the free TRA. The results of in vitro EGF-induced and H2O2-induced models suggested that TCeO2-TRA-FNL effectively reduced the level of inflammation and alleviated oxidative stress in HaCat cells. The results of in vivo imiquimod (IMQ)-induced model indicated that TCeO2-TRA-FNL-Gel could greatly alleviate the psoriasis symptoms. In summary, the transdermal drug delivery system designed in this study has shown excellent therapeutic effects on psoriasis and is prospective for the safe and accurate therapy of psoriasis.
Ferroptosis in Parkinson's disease: Molecular mechanisms and therapeutic potential
Authors: Xv-shen Ding, Li Gao, Zheng Han, Simona Eleuteri, Wei Shi, Yun Shen, Zi-yao Song, Mingming Su, Qian Yang, Yan Qu, David K. Simon, Xue-lian Wang, Bao Wang
Journal: Ageing Research Reviews (2023)
Comparison of virus-capsid mimicking biologic-shell based versus polymeric-shell nanoparticles for enhanced oral insulin delivery
Authors: Zhixiang Cui, Shuman Cui, Lu Qin, Yalin An, Xin Zhang, Jian Guan, Tin Wui Wong, Shirui Mao
Journal: Asian Journal of Pharmaceutical Sciences (2023)

Virus-capsid mimicking mucus-permeable nanoparticles are promising oral insulin carriers which surmount intestinal mucus barrier. However, the impact of different virus-capsid mimicking structure remains unexplored. In this study, utilizing biotin grafted chitosan as the main skeleton, virus-mimicking nanoparticles endowed with biologic-shell (streptavidin coverage) and polymeric-shell (hyaluronic acid/alginate coating) were designed with insulin as a model drug by self-assembly processes. It was demonstrated that biologic-shell mimicking nanoparticles exhibited a higher intestinal trans-mucus (>80%, 10 min) and transmucosal penetration efficiency (1.6-2.2-fold improvement) than polymeric-shell counterparts. Uptake mechanism studies revealed caveolae-mediated endocytosis was responsible for the absorption of biologic-shell mimicking nanoparticles whereas polymeric-shell mimicking nanoparticles were characterized by clathrin-mediated pathway with anticipated lysosomal insulin digestion. Further, in vivo hypoglycemic study indicated that the improved effect of regulating blood sugar levels was virus-capsid structure dependent out of which biologic-shell mimicking nanoparticles presented the best performance (5.1%). Although the findings of this study are encouraging, much more work is required to meet the standards of clinical translation. Taken together, we highlight the external structural dependence of virus-capsid mimicking nanoparticles on the muco-penetrating and uptake mechanism of enterocytes that in turn affecting their in vivo absorption, which should be pondered when engineering virus-mimicking nanoparticles for oral insulin delivery.